Ultrasonic energy has been used to disperse agglomerates of a variety of materials such as food ingredients, pharmaceutical ingredients, and industrial materials. Some traditional uses of ultrasonic energy in pharmaceutical ingredients include processes of de-agglomeration, compacting, and atomization. However, ultrasonic energy has not been used to prepare pharmaceutically active materials having a monomodal size distribution.
Depending on the active pharmaceutical and its targeted use, one dissolution profile may be more desirable than another dissolution profile. Some drugs should have a constant, flat dissolution profile, while other drugs should have a dissolution profile with one or more peak dissolution points. Conventional active pharmaceutical materials, as synthesized or as provided from a manufacturer of raw active pharmaceuticals, have a wide distribution of particle sizes and are not characterized as having monomodal, bimodal, or multimodal particle size distributions. Particle size distributions are not typically considered or controlled during the manufacture (synthesis) of raw pharmaceutically active materials. Moreover, screening without ultrasonic energy does not provide the desired monomodal particle size distribution and does not provide the desired reproducible dissolution profile since the raw pharmaceutically active particulate materials tend to agglomerate. These agglomerates pass through screens along with non-agglomerate large particles, but since the agglomerates consist of a collection of smaller active particles held together by electrostatic attraction, the particle size distribution is not monomodal.
Obtaining and consistently reproducing a desired dissolution profile has been a difficult or impossible problem to solve due to inconsistencies in particle size distribution of the active material. Excipients, granule coatings, and tablet compression have been used by others to attempt to control the dissolution profile of pharmaceutical dosage forms. These attempts have not always been as successful as desired because they do not fully and/or directly address an underlying source of difficulty relating to particle size distribution consistency.